JP4361733B2 - ウィルス核酸のインビトロにおける増幅方法及び当該増幅方法を行うことによる腫瘍細胞のインビトロにおける破壊方法 - Google Patents
ウィルス核酸のインビトロにおける増幅方法及び当該増幅方法を行うことによる腫瘍細胞のインビトロにおける破壊方法 Download PDFInfo
- Publication number
- JP4361733B2 JP4361733B2 JP2002555221A JP2002555221A JP4361733B2 JP 4361733 B2 JP4361733 B2 JP 4361733B2 JP 2002555221 A JP2002555221 A JP 2002555221A JP 2002555221 A JP2002555221 A JP 2002555221A JP 4361733 B2 JP4361733 B2 JP 4361733B2
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- promoter
- adenovirus
- vitro
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 123
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 97
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 97
- 238000000034 method Methods 0.000 title claims description 31
- 210000004881 tumor cell Anatomy 0.000 title claims description 30
- 230000003612 virological effect Effects 0.000 title claims description 27
- 238000000338 in vitro Methods 0.000 title claims description 22
- 238000003199 nucleic acid amplification method Methods 0.000 title claims description 18
- 230000003321 amplification Effects 0.000 title claims description 17
- 230000006378 damage Effects 0.000 title claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 20
- 101710114676 E1B 55 kDa protein Proteins 0.000 claims description 12
- 230000003213 activating effect Effects 0.000 claims description 2
- 241000701161 unidentified adenovirus Species 0.000 description 86
- 108010048626 Y-Box-Binding Protein 1 Proteins 0.000 description 83
- 102100022224 Y-box-binding protein 1 Human genes 0.000 description 79
- 206010028980 Neoplasm Diseases 0.000 description 52
- 108090000623 proteins and genes Proteins 0.000 description 36
- 239000013598 vector Substances 0.000 description 28
- 230000010076 replication Effects 0.000 description 27
- 241000700605 Viruses Species 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 210000004940 nucleus Anatomy 0.000 description 25
- 230000014509 gene expression Effects 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 14
- 230000022131 cell cycle Effects 0.000 description 13
- 230000032258 transport Effects 0.000 description 13
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 12
- 238000012217 deletion Methods 0.000 description 12
- 230000037430 deletion Effects 0.000 description 12
- 230000002950 deficient Effects 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 10
- 108010017842 Telomerase Proteins 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 239000012634 fragment Substances 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 108700019146 Transgenes Proteins 0.000 description 7
- 230000002238 attenuated effect Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000009089 cytolysis Effects 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 210000003855 cell nucleus Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 5
- 241000714474 Rous sarcoma virus Species 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000029812 viral genome replication Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 4
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 101800001144 Arg-vasopressin Proteins 0.000 description 3
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 3
- 102100035182 Plastin-2 Human genes 0.000 description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 3
- 108700005077 Viral Genes Proteins 0.000 description 3
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000036457 multidrug resistance Effects 0.000 description 3
- 108010049148 plastin Proteins 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 101150084750 1 gene Proteins 0.000 description 2
- 241000701242 Adenoviridae Species 0.000 description 2
- 108010056962 Adenovirus E4 Proteins Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101150082674 E2 gene Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 108700019961 Neoplasm Genes Proteins 0.000 description 2
- 102000048850 Neoplasm Genes Human genes 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 102000011931 Nucleoproteins Human genes 0.000 description 2
- 108010061100 Nucleoproteins Proteins 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 102100032938 Telomerase reverse transcriptase Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108010079351 Tumor Suppressor Protein p14ARF Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 102000009266 Y-Box-Binding Protein 1 Human genes 0.000 description 2
- 108700010877 adenoviridae proteins Proteins 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000000234 capsid Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 231100000024 genotoxic Toxicity 0.000 description 2
- 230000001738 genotoxic effect Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000005033 mesothelial cell Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000012223 nuclear import Effects 0.000 description 2
- 230000025308 nuclear transport Effects 0.000 description 2
- 244000309459 oncolytic virus Species 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 108700025694 p53 Genes Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 229940123373 Adenovirus E1A gene Drugs 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 101100437895 Alternaria brassicicola bsc3 gene Proteins 0.000 description 1
- 102000019063 CCAAT-Binding Factor Human genes 0.000 description 1
- 108010026988 CCAAT-Binding Factor Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 101710199711 Early E1A protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241001135569 Human adenovirus 5 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 101710192606 Latent membrane protein 2 Proteins 0.000 description 1
- 101150066553 MDR1 gene Proteins 0.000 description 1
- 108010066154 Nuclear Export Signals Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 101150073872 ORF3 gene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 101100226891 Phomopsis amygdali PaP450-1 gene Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 101150080074 TP53 gene Proteins 0.000 description 1
- 101710109576 Terminal protein Proteins 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 1
- 102100033254 Tumor suppressor ARF Human genes 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000006743 cytoplasmic accumulation Effects 0.000 description 1
- -1 daunoblastine Chemical compound 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 241001492478 dsDNA viruses, no RNA stage Species 0.000 description 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000006355 external stress Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000000174 oncolytic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000006490 viral transcription Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Plant Pathology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Description
B−55」等とも記載する)であることを特徴とする、前記第3のウィルス核酸のインビトロにおける増幅方法である。
腫瘍組織のサンプルを調べるステップと、
細胞周期とは無関係にYB−1が核内に存在するかどうかを決定するステップと
を含む方法に関する。
YB−1がE2後期プロモーターによるE2の発現を制御することを示すために、次の実験手法を実施した。
YB−1がE2後期プロモーターによるE2の発現を制御することを示すために、実施例1に記載のプロトコルに基づく次の実験手法を実施した。
この実験は、転写因子であるYB−1がE2後期プロモーター内のYボックス(CAAT配列)に結合するはずである、という予想に基づいている。YB−1とこのプロモーターとの特異的な結合を検出するために、いわゆるEMSA分析(electrophoretic mobility shift assay)を行う。即ち、野生型アデノウィルスを細胞に感染させた24時間後に核タンパクを単離する。次いで、当該核タンパク(1〜10μg)とE2後期プロモーター配列を含む短いDNAフラグメント(長さ:30〜80ベース)とを共に37℃で30分間インキュベートする。このDNAフラグメント(オリゴ)を、前もって5’末端においてキナーゼを用いて32Pで放射性標識する。その後、そのままの(native)ポリアクリルアミドゲルを用いて分離する。タンパクYB−1が該オリゴの配列と結合する場合、5’末端において放射性標識された短いDNAフラグメントは、YB−1がその短いDNAフラグメントと結合しているために、未結合のオリゴよりもゆっくりとゲル内で移動するため、いわゆるシフトが見られる。このシフトは、100倍過剰の未標識のオリゴを反応混合物に添加するとすぐに、再び消失させることができる。
Claims (9)
- YB−1をコードする核酸配列を含むアデノウィルス核酸を、人体から分離された腫瘍細胞に感染させて、当該腫瘍細胞におけるアデノウィルス核酸の増幅を行うことを特徴とする、ウィルス核酸のインビトロにおける増幅方法。
- アデノウィルス核酸におけるE1をコードする核酸配列が欠損し又は不活性化されていることを特徴とする、請求項1に記載のウィルス核酸のインビトロにおける増幅方法。
- E1がE1Bであることを特徴とする、請求項2記載のウィルス核酸のインビトロにおける増幅方法。
- E1Bが、E1B55kDaタンパク質であることを特徴とする、請求項3記載のウィルス核酸のインビトロにおける増幅方法。
- アデノウィルス核酸におけるE1Aをコードする核酸配列が欠損し又は不活性化されていることを特徴とする、請求項1〜4のいずれかに記載のウィルス核酸のインビトロにおける増幅方法。
- アデノウィルス核酸を増幅させる腫瘍細胞の核内にYB−1が存在することを特徴とする、請求項2〜5のいずれかに記載のウィルス核酸のインビトロにおける増幅方法。
- アデノウィルス核酸の増幅が、YB−1によるE2プロモーターの活性化により行われることを特徴とする、請求項1〜6のいずれかに記載のウィルス核酸のインビトロにおける増幅方法。
- E2プロモーターが、後期E2プロモーターであることを特徴とする、請求項7に記載のウィルス核酸のインビトロにおける増幅方法。
- 請求項1〜8のいずれかに記載のウィルス核酸のインビトロにおける増幅方法を、人体から分離された腫瘍細胞内にて行うことにより、当該腫瘍細胞を破壊することを特徴とする、腫瘍細胞のインビトロにおける破壊方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2000165504 DE10065504A1 (de) | 2000-12-28 | 2000-12-28 | Adenovirale Systeme und deren Anwendungen |
DE2001150945 DE10150945A1 (de) | 2001-10-16 | 2001-10-16 | Adenovirale Systeme und deren Anwendungen |
PCT/EP2001/015212 WO2002053711A2 (de) | 2000-12-28 | 2001-12-21 | Verwendung des transkriptionsfaktors yb-1 in adenoviralen systemen |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008096110A Division JP4361954B2 (ja) | 2000-12-28 | 2008-04-02 | アデノウィルス核酸を含有する医薬用組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2004535768A JP2004535768A (ja) | 2004-12-02 |
JP4361733B2 true JP4361733B2 (ja) | 2009-11-11 |
Family
ID=26008118
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002555221A Expired - Fee Related JP4361733B2 (ja) | 2000-12-28 | 2001-12-21 | ウィルス核酸のインビトロにおける増幅方法及び当該増幅方法を行うことによる腫瘍細胞のインビトロにおける破壊方法 |
JP2008096110A Expired - Fee Related JP4361954B2 (ja) | 2000-12-28 | 2008-04-02 | アデノウィルス核酸を含有する医薬用組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008096110A Expired - Fee Related JP4361954B2 (ja) | 2000-12-28 | 2008-04-02 | アデノウィルス核酸を含有する医薬用組成物 |
Country Status (9)
Country | Link |
---|---|
US (2) | US8263067B2 (ja) |
EP (1) | EP1346058B1 (ja) |
JP (2) | JP4361733B2 (ja) |
AT (1) | ATE361369T1 (ja) |
AU (1) | AU2002229679B2 (ja) |
CA (1) | CA2433071C (ja) |
DE (1) | DE50112463D1 (ja) |
ES (1) | ES2287181T3 (ja) |
WO (1) | WO2002053711A2 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5213298B2 (ja) | 2002-05-27 | 2013-06-19 | ホルム,ペル・ゾンネ | アデノウイルスおよびそれをコードしている核酸の新たな使用 |
AU2003271730A1 (en) * | 2002-10-15 | 2004-05-04 | Per Sonne Holm | Novel adenoviruses, nucleic acids coding therefor, and use thereof |
PL219321B1 (pl) * | 2002-10-15 | 2015-04-30 | Per Sonne Holm | Adenowirus, kodujący go kwas nukleinowy, zawierający je układ replikacyjny, wektor, komórka i organizm, ich zastosowanie oraz środek farmaceutyczny |
WO2004066947A2 (en) * | 2003-01-28 | 2004-08-12 | Shanghai Sunway Biotech Co., Ltd. | Hyperthermia oncolysis co-therapy |
WO2005051430A1 (de) | 2003-11-14 | 2005-06-09 | Per Sonne Holm | Neue verwendung von adenoviren und dafür codierenden nukleinsäuren |
CA2590257A1 (en) * | 2003-11-14 | 2005-06-09 | Per Sonne Holm | Novel adenoviruses, nucleic acids that code for the same and the use of said viruses |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5846945A (en) | 1993-02-16 | 1998-12-08 | Onyx Pharmaceuticals, Inc. | Cytopathic viruses for therapy and prophylaxis of neoplasia |
US5698443A (en) | 1995-06-27 | 1997-12-16 | Calydon, Inc. | Tissue specific viral vectors |
US6676935B2 (en) * | 1995-06-27 | 2004-01-13 | Cell Genesys, Inc. | Tissue specific adenoviral vectors |
US6022863A (en) * | 1996-05-21 | 2000-02-08 | Yale University | Regulation of gene expression |
WO1998021350A1 (en) * | 1996-11-13 | 1998-05-22 | Board Of Regents, The University Of Texas System | Diminishing viral gene expression by promoter replacement |
WO1999006576A1 (en) * | 1997-08-04 | 1999-02-11 | Calydon, Inc. | A human glandular kallikrein enhancer, vectors comprising the enhancer and methods of use thereof |
KR100266901B1 (ko) * | 1997-09-04 | 2000-10-02 | 윤종용 | 내부 전원 전압 발생 회로 및 그것을 이용한 반도체 메모리 장치 |
WO2000039320A1 (en) * | 1998-12-23 | 2000-07-06 | Genentech, Inc. | Transfectacons comprising calcium phosphate and a nucleic acid |
DE19860602A1 (de) | 1998-12-29 | 2000-07-06 | Max Delbrueck Centrum | Gentransfervektor für die Diagnostik und die Therapie von malignen Tumoren |
GB9906815D0 (en) * | 1999-03-24 | 1999-05-19 | Isrec | Anti-neoplastic viral agents |
DE19929569A1 (de) * | 1999-06-21 | 2000-12-28 | Holm Per Sonne | Mittel zur Behandlung maligner Erkrankungen unter Verwendung des Proteins YB-1 |
WO2001002556A2 (de) * | 1999-06-30 | 2001-01-11 | Max-Delbrück-Centrum für Molekulare Medizin | Mittel zur diagnose, prognose und therapie maligner erkrankungen |
US6140126A (en) * | 1999-10-26 | 2000-10-31 | Isis Pharmaceuticals Inc. | Antisense modulation of Y-box binding protein 1 expression |
IT1318694B1 (it) | 2000-09-13 | 2003-08-27 | Monica Rota | Dispositivo per il rilevamento di dati cranio-facciali, in riferimentoad un piano fisso. |
AU784975B2 (en) * | 2000-10-11 | 2006-08-10 | Sumitomo Chemical Company, Limited | DNA-binding protein YB-1-containing collagen accumulation inhibitors |
US20030095989A1 (en) * | 2000-12-18 | 2003-05-22 | Irving John M. | Chimeric cytolytic viruses for cancer treatment |
-
2001
- 2001-12-21 EP EP01990586A patent/EP1346058B1/de not_active Expired - Lifetime
- 2001-12-21 JP JP2002555221A patent/JP4361733B2/ja not_active Expired - Fee Related
- 2001-12-21 CA CA2433071A patent/CA2433071C/en not_active Expired - Lifetime
- 2001-12-21 DE DE50112463T patent/DE50112463D1/de not_active Expired - Lifetime
- 2001-12-21 AT AT01990586T patent/ATE361369T1/de active
- 2001-12-21 WO PCT/EP2001/015212 patent/WO2002053711A2/de active IP Right Grant
- 2001-12-21 AU AU2002229679A patent/AU2002229679B2/en not_active Expired
- 2001-12-21 US US10/451,210 patent/US8263067B2/en not_active Expired - Lifetime
- 2001-12-21 ES ES01990586T patent/ES2287181T3/es not_active Expired - Lifetime
-
2008
- 2008-04-02 JP JP2008096110A patent/JP4361954B2/ja not_active Expired - Fee Related
-
2009
- 2009-02-09 US US12/368,121 patent/US20100330037A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
JP2004535768A (ja) | 2004-12-02 |
JP4361954B2 (ja) | 2009-11-11 |
US20100330037A1 (en) | 2010-12-30 |
ES2287181T3 (es) | 2007-12-16 |
WO2002053711A3 (de) | 2003-01-23 |
AU2002229679B2 (en) | 2007-12-20 |
CA2433071C (en) | 2011-02-15 |
JP2008237219A (ja) | 2008-10-09 |
EP1346058B1 (de) | 2007-05-02 |
ATE361369T1 (de) | 2007-05-15 |
EP1346058A2 (de) | 2003-09-24 |
DE50112463D1 (de) | 2007-06-14 |
CA2433071A1 (en) | 2002-07-11 |
US8263067B2 (en) | 2012-09-11 |
US20040067586A1 (en) | 2004-04-08 |
WO2002053711A2 (de) | 2002-07-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6817979B2 (ja) | 腫瘍選択的e1aおよびe1b変異体 | |
US11268073B2 (en) | Use of adenovirus and nucleic acids coding therefor | |
AU2010257327B2 (en) | Adenovirus expressing genes in reverse order and use thereof | |
JP4361954B2 (ja) | アデノウィルス核酸を含有する医薬用組成物 | |
CA2515650C (en) | New adenoviruses, nucleic acids coding therefor and their use | |
AU2015201828B2 (en) | Novel use of adenoviruses and nucleic acids coding therefor |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A529 | Written submission of copy of amendment under article 34 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A529 Effective date: 20030826 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041210 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071002 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20071227 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080109 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080403 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080515 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081224 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090309 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090316 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090623 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090721 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090813 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4361733 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120821 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120821 Year of fee payment: 3 |
|
R154 | Certificate of patent or utility model (reissue) |
Free format text: JAPANESE INTERMEDIATE CODE: R154 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120821 Year of fee payment: 3 |
|
R154 | Certificate of patent or utility model (reissue) |
Free format text: JAPANESE INTERMEDIATE CODE: R154 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130821 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |